Prognostic Biomarkers in Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnoses worldwide and remains a leading cause of cancer-related mortality. Prognostic biomarkers are measurable indicators that predict disease course, survival and likelihood of treatment benefit. Traditional tissue-based markers such as programmed death-ligand 1 expression and tumour mutational burden offer insight into therapeutic response but are limited by sampling bias and intratumour heterogeneity. Blood-based measures including inflammatory indices have emerged as readily accessible surrogates of tumour biology and host immunity. Ratios of circulating cell populations, acute-phase proteins and cytokines reflect systemic inflammation and immunosuppression, correlating with progression-free and overall survival. Advances in liquid biopsy now enable detection of circulating tumour DNA and tumour-derived vesicles, providing dynamic assessment of molecular alterations and minimal residual disease. Multiparametric nomograms integrate clinical, laboratory and molecular variables into graphical models that refine risk stratification for individual patients. Despite rapid growth in candidate biomarkers, standardisation of assay platforms, validation in diverse cohorts and clear differentiation between prognostic and predictive roles remain challenges. Continued harmonisation of methodologies and prospective evaluation in clinical trials are essential to translate biomarker discoveries into routine practice and to personalise management for patients with NSCLC.

Research from Nature Portfolio

Comprehensive immune profiling of NSCLC tissue using high-dimensional cytometry has revealed that neutrophils represent the dominant infiltrating cell type, with marked differences between adenocarcinoma and squamous cell subtypes. These findings underscore the role of myeloid populations in shaping prognosis and guiding immunotherapy trial design. In parallel, a retrospective pan-cancer analysis demonstrated that a low neutrophil-to-lymphocyte ratio (NLR) combined with high tumour mutational burden (TMB) identifies patients most likely to benefit from checkpoint inhibitors, offering a cost-effective stratification tool. A meta-analysis of 14 studies further confirmed that elevated pretreatment NLR portends poorer overall and progression-free survival in NSCLC, establishing NLR as a robust, widely accessible prognostic biomarker across clinical settings.

Prognostic Biomarkers in Non-Small Cell Lung Cancer publication trend

The graph below shows the total number of articles in prognostic biomarkers in non-small cell lung cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Non-small cell lung cancer (NSCLC): A group of lung cancers including adenocarcinoma and squamous cell carcinoma that together account for most lung cancer cases.

Neutrophil-to-lymphocyte ratio (NLR): The ratio of circulating neutrophils to lymphocytes, used as an indicator of systemic inflammation and immune status.

Tumour mutational burden (TMB): The total number of somatic mutations per coding area of a tumour genome, reflecting neoantigen load.

Circulating tumour DNA (ctDNA): Fragments of tumour-derived DNA found in the bloodstream, used for non-invasive molecular profiling and disease monitoring.

C-reactive protein (CRP): An acute-phase protein produced by the liver in response to inflammation, serving as a general marker of systemic inflammatory activity.

Interleukin-6 (IL-6): A pro-inflammatory cytokine that modulates immune responses and can promote tumour growth and resistance to therapy.

Nomogram: A graphical predictive model that integrates multiple variables to estimate the probability of a clinical event, such as survival.

References

1. Increased interleukin-6/C-reactive protein levels are associated with the upregulation of the adenosine pathway and serve as potential markers of therapeutic resistance to immune checkpoint inhibitor-based therapies in non-small cell lung cancer. Journal for ImmunoTherapy of Cancer (2023).
2. Soluble biomarkers to predict clinical outcomes in non-small cell lung cancer treated by immune checkpoints inhibitors. Frontiers in Immunology (2023).
3. New biomarkers exploration and nomogram construction of prognostic and immune-related adverse events of advanced non-small cell lung cancer patients receiving immune checkpoint inhibitors. Respiratory Research (2023).
4. Neutrophils dominate the immune cell composition in non-small cell lung cancer. Nature Communications (2017).
5. Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors. Nature Communications (2021).
6. Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer: a meta-analysis. Scientific Reports (2015).